The broad goal of this work is to use the C. elegans model system to understand the genetic and molecular mechanisms underlying the developmental regulation of microRNA expression. There are more than 150 distinct microRNA genes in C. elegans, including more than 20 families of microRNAs with homologs in humans. The functions of these are largely unknown, although it is clear that microRNAs play important roles in a wide spectrum of developmeental and phsyiologocal processes in all animals. Little is known about how microRNA gene expression is regulated transcriptionaly or post-transcriptionally by developmental and physiologiical signals. Molecular and genetic approaches will be employed to characterize mechanisms of microRNA transcriptional regulation in C.elegans, and to characterize the proteins and RNA elements responsible for post-transcriptional developmental regulation of microRNA biogenesis.